Three mouse strains in the C3H lineage, C3H/HeJ, C3HeB/FeJ and C3H/HeNCr1BR, which differ in their responsiveness of LPS and their innate susceptibilities to Salmonella infection, will be used to investigate immunity to Salmonella infection induced by a live, a virulent vaccine strain, SL3235, that is of a class of mutants being considered for development of a new vaccine for human typhoid fever. The mechanisms by which the vaccine results in specific resistance to virulent Salmonella infection will be assessed, as will the immunomodulation induced by this organism. The degree of macrophage activation to tumoricidal and microbicidal capacity will be compared with that engendered by killed Salmonella, BCG and C. parvum. The role of suppressor macrophages in modulating the humoral and cellular arms of the immune response will be investigated, as will molecular correlates of macrophage activation and suppression as measured by production of PGE-2, IL-1, H202, and 02. These studies should provide basic information on immunity to Salmonella infection, evaluate the potential of SL3235 as an immunomodulating agent, and possibly provide insight into the nature of the defect in macrophages of C3H/HeJ mice.